To date, the exploration of multi-principal element alloys (MPEAs) has rarely ventured into the realm of hexagonal close-packed (HCP) structures. In this research, we embarked on a pioneering systematic comparison between a single-phase Ti-Zr-Hf HCP-MPEA and Ti regarding their dislocation activities and mesoscale deformation homogeneity. Through large-area high-resolution quasi-in-situ slip trace analysis and crystal plasticity finite element modeling, we identified HCP-MPEA’s significantly enhanced pyramidal slip activities—resulted from minimized disparities among different deformation modes—notably improve the material’s intragranular deformation homogeneity. Alongside MPEA’s intrinsically high slip resistance, it renders HCP-MPEA an outstanding strength-toughness combination relative to its conventional HCP counterparts.